Abstract 635: Concordance between dogs and humans: The use of AI in evaluating clinical cancer genomic datasets
Authors: Kevin Wu, Lucas Rodrigues, Gerald Post, Garrett Harvey, Aubrey Miller, Lindsay Lambert, Christina Lopes, Benjamin Lewis, James Zou
Journal: Cancer Research (2022)

Abstract Spontaneous tumors in dogs are highly similar to human cancers histologically, genetically, molecularly and clinically. In this presentation we explore similarities found across species when associating cancer biomarkers and outcomes. Our findings validate concordance across the cancer journeys. This is important to deepen the field of comparative oncology and affirming spontaneous cancer in dogs as an ideal ‘model’ for precision oncology, building upon recent work in tumor biology concordance. Our machine learning analysis prognosis and predictive effect of genomic alterations in 1303 client-owned tumor-bearing dogs identified TP53 and PTPRD as prognostic markers for poor survival in dogs with an overall survival hazard ratio (OS HR) of 1.732, 1.914, respectively (P&amp;lt;0.001 and P=0.023). These results are aligned with non-small cell lung cancer, metastatic breast cancer and pancreatic cancer in people correlated with poor survival when carrying TP53 mutation, and PTPRD also correlated with poor survival in gliomas. Besides that, we also identified ALB1 and PIK3CA prognostic markers for poor survival in canine tumors with an overall survival hazard ratio (OS HR) of 1.707, 1.689, respectively (P=0.01, and P=0.002). This data reaffirms the similarity between canine and human cancers not just in the genomic profiles but also the tumor biology and treatment strategy for both species. Among tumor types, lymphoma and hemangiosarcoma showed the worst survival times (N=32, OS HR=1.929, P=0.002, and N=202, OS HR=1.743, P&amp;lt;0.001). Interestingly, we also identified that dogs with RET mutations respond better to toceranib, a veterinary oral multikinase inhibitor against RET, VEGFR2, PDGFR, FLT3 and c-KIT; this is in concordance with sunitinib a tyrosine kinase inhibitor that target RET used in humans thyroid carcinomas and other tumors carrying RET mutations. To the best of our knowledge, this is the largest canine tumor clinical genomic dataset analysis. Applying real-world evidence and data tools in the FidoCure® dataset, we successfully identified associations between gene mutations and survival associated with response to target therapy treatment. These associations can benefit dogs by enabling better therapeutic recommendations and also benefit human cancer research since canine models recapitulate human disease with intact immune systems and similar tumor genomic profiles, confirmed by the FidoCure® database, accelerating clinical studies of novel treatments that currently have significant barriers to study at scale. Citation Format: Kevin Wu, Lucas Rodrigues, Gerald Post, Garrett Harvey, Aubrey Miller, Lindsay Lambert, Christina Lopes, Benjamin Lewis, James Zou. Concordance between dogs and humans: The use of AI in evaluating clinical cancer genomic datasets [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 635.